CA2501565A1 - Procede de phosphitylation - Google Patents
Procede de phosphitylation Download PDFInfo
- Publication number
- CA2501565A1 CA2501565A1 CA002501565A CA2501565A CA2501565A1 CA 2501565 A1 CA2501565 A1 CA 2501565A1 CA 002501565 A CA002501565 A CA 002501565A CA 2501565 A CA2501565 A CA 2501565A CA 2501565 A1 CA2501565 A1 CA 2501565A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- substituted
- process according
- unsubstituted
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract 16
- 238000005731 phosphitylation reaction Methods 0.000 title claims abstract 6
- 239000012190 activator Substances 0.000 claims abstract 7
- 150000007530 organic bases Chemical class 0.000 claims abstract 5
- 239000003795 chemical substances by application Substances 0.000 claims abstract 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract 3
- 239000002777 nucleoside Substances 0.000 claims abstract 3
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract 2
- 150000003839 salts Chemical class 0.000 claims abstract 2
- 125000001424 substituent group Chemical group 0.000 claims abstract 2
- 125000001931 aliphatic group Chemical group 0.000 claims 6
- 150000001875 compounds Chemical class 0.000 claims 5
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 claims 4
- 241000368571 Opsanus beta Species 0.000 claims 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 4
- 125000000623 heterocyclic group Chemical group 0.000 claims 4
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims 3
- 125000003118 aryl group Chemical group 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims 2
- 125000006241 alcohol protecting group Chemical group 0.000 claims 2
- 125000006242 amine protecting group Chemical group 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- AKYWYZQZJQIVEU-UHFFFAOYSA-N N-[2,2-bis[di(propan-2-yl)amino]propoxyphosphanyl]-2,2,2-trifluoroacetamide Chemical compound C(C)(C)N(C(C)C)C(COPNC(C(F)(F)F)=O)(C)N(C(C)C)C(C)C AKYWYZQZJQIVEU-UHFFFAOYSA-N 0.000 claims 1
- RFJDCAMETMDBBK-UHFFFAOYSA-N N-[2-benzhydrylsilylethoxy-[di(propan-2-yl)amino]phosphanyl]-N-propan-2-ylpropan-2-amine Chemical compound C=1C=CC=CC=1C([SiH2]CCOP(N(C(C)C)C(C)C)N(C(C)C)C(C)C)C1=CC=CC=C1 RFJDCAMETMDBBK-UHFFFAOYSA-N 0.000 claims 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- YKLJUGWFWPZZFA-UHFFFAOYSA-N amino-(morpholin-4-ylamino)phosphinous acid Chemical compound NP(O)NN1CCOCC1 YKLJUGWFWPZZFA-UHFFFAOYSA-N 0.000 claims 1
- 125000004475 heteroaralkyl group Chemical group 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 150000003573 thiols Chemical class 0.000 abstract 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 1
- 150000001298 alcohols Chemical class 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 125000003835 nucleoside group Chemical group 0.000 abstract 1
- 150000008300 phosphoramidites Chemical class 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 0 **(C=C1)C=CC(S(N2)(=O)=O)=C1C2=* Chemical compound **(C=C1)C=CC(S(N2)(=O)=O)=C1C2=* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/24—Esteramides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne un procédé destiné à la phosphitylation d'un alcool ou d'un thiol avec un agent de phosphitylation en présence d'un activateur. Cet activateur est représenté par la formule générale (1) dans laquelle p vaut 0 ou désigne un entier compris entre 1 et 4 et R désigne un substituant. De préférence, X?7¿ désigne O et p vaut 0. L'activateur est généralement utilisé comme un complexe de sel avec une base organique. Les alcools et les thiols préférés comprennent des nucléosides et des oligonucléotides. Le procédé est particulièrement adapté pour la synthèse de phosphoramidites.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US41818502P | 2002-10-15 | 2002-10-15 | |
US60/418,185 | 2002-10-15 | ||
PCT/GB2003/004312 WO2004035599A1 (fr) | 2002-10-15 | 2003-10-08 | Procede de phosphitylation |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2501565A1 true CA2501565A1 (fr) | 2004-04-29 |
CA2501565C CA2501565C (fr) | 2011-03-15 |
Family
ID=32107901
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2501565A Expired - Lifetime CA2501565C (fr) | 2002-10-15 | 2003-10-08 | Procede de phosphitylation |
Country Status (10)
Country | Link |
---|---|
US (1) | US7247720B2 (fr) |
EP (1) | EP1554300B1 (fr) |
JP (1) | JP4756863B2 (fr) |
KR (1) | KR101065715B1 (fr) |
CN (1) | CN1329408C (fr) |
AT (1) | ATE362937T1 (fr) |
AU (1) | AU2003269239A1 (fr) |
CA (1) | CA2501565C (fr) |
DE (1) | DE60313993T2 (fr) |
WO (1) | WO2004035599A1 (fr) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR036122A1 (es) * | 2001-07-03 | 2004-08-11 | Avecia Biotechnology Inc | Un complejo de sal que comprende un n-alquilimidazol y una 1,1-dioxo-1,2-dihidro-1l6-benzo [d]-isotiazol-3-ona y un metodo para sintetizar oligonucleotidos utilizando la quimica de fosforamidita |
GB0229443D0 (en) * | 2002-12-18 | 2003-01-22 | Avecia Ltd | Process |
JPWO2021141072A1 (fr) * | 2020-01-08 | 2021-07-15 | ||
JPWO2023140040A1 (fr) * | 2022-01-21 | 2023-07-27 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5034534A (en) * | 1988-07-15 | 1991-07-23 | E. I. Du Pont De Nemours And Company | Process for producing saccharin, saccharin analogues or their salts |
US5662111A (en) * | 1991-01-28 | 1997-09-02 | Cosman; Eric R. | Process of stereotactic optical navigation |
US6034534A (en) * | 1995-05-25 | 2000-03-07 | Kiyota; Shigeo | Laminated contact probe for inspection of ultra-microscopic pitch |
US6274725B1 (en) * | 1998-06-02 | 2001-08-14 | Isis Pharmaceuticals, Inc. | Activators for oligonucleotide synthesis |
AR036122A1 (es) * | 2001-07-03 | 2004-08-11 | Avecia Biotechnology Inc | Un complejo de sal que comprende un n-alquilimidazol y una 1,1-dioxo-1,2-dihidro-1l6-benzo [d]-isotiazol-3-ona y un metodo para sintetizar oligonucleotidos utilizando la quimica de fosforamidita |
-
2003
- 2003-10-08 DE DE60313993T patent/DE60313993T2/de not_active Expired - Lifetime
- 2003-10-08 WO PCT/GB2003/004312 patent/WO2004035599A1/fr active IP Right Grant
- 2003-10-08 AT AT03751018T patent/ATE362937T1/de not_active IP Right Cessation
- 2003-10-08 CN CNB2003801014035A patent/CN1329408C/zh not_active Expired - Lifetime
- 2003-10-08 EP EP03751018A patent/EP1554300B1/fr not_active Expired - Lifetime
- 2003-10-08 KR KR1020057006226A patent/KR101065715B1/ko active IP Right Grant
- 2003-10-08 US US10/531,323 patent/US7247720B2/en not_active Expired - Lifetime
- 2003-10-08 JP JP2004544427A patent/JP4756863B2/ja not_active Expired - Lifetime
- 2003-10-08 CA CA2501565A patent/CA2501565C/fr not_active Expired - Lifetime
- 2003-10-08 AU AU2003269239A patent/AU2003269239A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
CA2501565C (fr) | 2011-03-15 |
AU2003269239A1 (en) | 2004-05-04 |
ATE362937T1 (de) | 2007-06-15 |
KR101065715B1 (ko) | 2011-09-19 |
US20060069247A1 (en) | 2006-03-30 |
US7247720B2 (en) | 2007-07-24 |
EP1554300B1 (fr) | 2007-05-23 |
EP1554300A1 (fr) | 2005-07-20 |
WO2004035599A1 (fr) | 2004-04-29 |
DE60313993D1 (de) | 2007-07-05 |
DE60313993T2 (de) | 2008-01-24 |
KR20050055004A (ko) | 2005-06-10 |
JP2006508081A (ja) | 2006-03-09 |
CN1329408C (zh) | 2007-08-01 |
CN1705675A (zh) | 2005-12-07 |
JP4756863B2 (ja) | 2011-08-24 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKEX | Expiry |
Effective date: 20231010 |